Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T

Authors


  • PFR is a consultant for Novartis, Roche, and Kyowa Hakko. NA, YHS, JEJ, GdC, DH, and DO have no conflicts of interest to report.

Corresponding author:
Nivedita Agarwal, M.D.
The Brain Institute
University of Utah
383 Colorow Drive
Salt Lake City, UT 84102, USA
Fax: 801-585-5375
E-mail: niv_aga@yahoo.co.uk

Abstract

Agarwal N, Sung YH, Jensen JE, daCunha G, Harper D, Olson D, Renshaw PF. Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T.
Bipolar Disord 2010: 12: 825–833. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S.

Objectives:  Altered metabolism of membrane phospholipids has been implicated in bipolar disorder. In humans, uridine is an important precursor of cytidine diphosphate (CDP)-choline, which plays a critical role in phospholipid synthesis and is currently being evaluated as a potential treatment for bipolar depression.

Methods:  A total of 17 healthy males (mean age ± SD: 32.73 ± 7.2 years; range: 21.8–46.4 years) were enrolled in this study. Subjects underwent a 31-phosphorus magnetic resonance spectroscopy (31P-MRS) acquisition at baseline and then again after seven days of either 2 g of uridine or placebo administration. A two-dimensional chemical shift imaging 31P-MRS acquisition collected spectral data from a 4 × 4 cluster of voxels acquired in the axial plane encompassing the subcortical structures as well as frontal-temporal cortical gray and white matter. The slab thickness was 3 cm and the approximate total volume of brain sampled was 432 cm3. The spectra obtained were analyzed using a fully automated in-house fitting algorithm. A population-averaged generalized estimating equation was used to evaluate changes both in phosphomonoesters (PME) [phosphocholine (PCho) and phosphoethanolamine (PEtn)] and phosphodiesters (PDE) [glycerophosphocholine (GPCho) and glycerophosphethanolamine (GPEtn)]. Metabolite ratios were reported with respect to the total integrated 31P resonance area.

Results:  The uridine group had significantly increased total PME and PEtn levels over the one-week period [6.32 and 7.17% for PME and PEtn, respectively (p < 0.001)]. Other metabolite levels such as PCho, PDE, GPEtn and GPCho showed no significant changes following either uridine or placebo (all p > 0.05).

Conclusions:  This is the first study to report a direct effect of uridine on membrane phospholipid precursors in healthy adults using 31P-MRS. Sustained administration of uridine appears to increase PME in healthy subjects. Further investigation is required to clarify the effects of uridine in disorders with altered phospholipid metabolism such as bipolar disorder.

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